Alzheimer's disease (AD) involves the production of deposits of a protein which is normally produced, amyloid beta-protein (Ab). Genetic evidence suggests Ab may play a causal role. But with the probable exception of increased Ab, none of the factors promoting Ab deposition in vivo have been demonstrated. The investigators have developed experimental paradigms for exploring the Ab deposition process, and identified several variables (one with a possible role in FAD) which appear to promote blockable Ab deposits in tat brain; they propose to characterize these phenomena in detail, and to test other factors which may seed or promote deposits in the same model system. They propose to also investigate factors which may promote plaque progression after deposition and to further investigate our preliminary ultrastructural and immunohistochemical evidence for toxicity and to determine the relationship between toxicity and the degree of Ab aggregation. These experiments will provide the first example of a system where endogenous Ab deposits can be induced by injury or growth factors in a rat model, and where an important and manipulative risk factor for AD may be demonstrated along with a specific inhibitor.